With increasing urbanization and climate change, the impact of heat on cardiovascular (CV) health of urban populations is a growing concern. Accordingly, the aim of this study was to quantify socio-urban vulnerability to heat (SU_VtoH) relevant to CV health in a major European urban area. CV vulnerability to heat (CV_VtoH) was defined as the proportion of CV emergencies that occurred at home during heat days in relation to all indoor CV emergencies. The SU_VtoH was calculated by weighting the values of non-residential buildings’ volume, green roofs, population density, land surface temperature, access to drinking water fountains, and/or fraction of elderly, female, and graduate residents with coefficients derived from spatial and non-spatial regression models. Subsequently, the SU_VtoH was normalized to reach values between 0 and 1, and global and local Moran’s I was used to test its clustering tendency. The SU_VtoH was calculated for the 86 districts of Milan, Italy. It reached a median equal to 0.596 (25th–75th percentile: 0.498–0.667) and showed a small significant tendency to cluster (global Moran's I equal to 0.147). Local Moran’s I identified 10 significant districts characterized by high SU_VtoH and surrounded by neighborhoods also exhibiting high SU_VtoH. In Milan, a total of 322,068 people live in 18 neighborhoods characterized by elevated values of both CV_VtoH and SU_VtoH. This proactive approach to SU_VtoH with a focus on CV health is consistent with global health goals by prioritizing resilient urban environments and protecting individuals before they require clinical intervention.